2. Noninvasive Positive Pressure Ventilation in Stable Chronic Alveolar Hypoventilation Syndromes BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINE Mansoura Faculty of Medicine

3. NPPV has been used in chronic alveolar hgypoventilation syndromes secondary to:- 1-Central respiratory control disturbances (CRCD). 2- Restrictive thoracic cage disorders (RTCD). 3- Neuromuscular diseases (NMD). 4-Obesity hypoventilation syndrome (OHS).

4. Application of NPPV via a mask interface avoids the morbidity involved with tracheostomy. The most common approach is delivery of bilevel positive airway pressure (BPAP) in which separately adjustable inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP) are delivered. The pressure support mode devices are inherently leak tolerant and therefore ideal for use with mask ventilation. NPPV using BPAP may be delivered in the spontaneous mode (S) in which the patient determines the time spent in IPAP (within the device IPAPtime limits) as well as the respiratory rate. NPPV in the spontaneous-timed (ST) mode provides a backup rate to ensure a minimum respiratory rate. If the patient fails to initiate an IPAP/EPAP cycle within a time window based on the backup rate, the device will deliver a machine-triggered IPAP cycle for the inspiratory time (IPAP time) set by the prescribing physician

5. The backup rate is 12, and as the patient did not trigger a breath for 5 seconds, a machine triggered breath was provided (A). Note that spontaneous and machine triggered breaths have similar peak flows (B, C) but different durations and different tidal volumes. The negative pressure spike (A) is an artifact generated by the NPPV device to denote a machine triggered breath.

6. NPPV is often initiated after an attended NPPV titration with PSG This approach allows determination of an appropriate interface, NPPV mode, IPAP, EPAP, as well as backup rate and inspiratory time (IPAP time), IPAP and EPAP can also be adjusted to eliminate obstructive apnea, hypopnea, RERAs, and snoring. Some sleep centers use transcutaneous PCO2 monitoring, end- tidal PCO2, or ABG sampling to guide adjustments to the NPPV device. Monitoring respiratory muscle EMG is performed in some sleep centers to help assess if adequate respiratory muscle rest has been attained during the titration.

7. When adequate NPPV was provided to this patient the diaphragmatic EMG (EMGdia) decreased as did the respiratory rate. Note the ECG artifact superimposed on the diaphragmatic EMG

8. NPPV devices used for titration with PSG Typically provide analog or digital outputs of flow, tidal volume, delivered pressure, and leak (total or unintentional depending on the manufacturer) that may be recorded along with other standard PSG information. The scope of these NPPV titration recommendations is restricted to adult patients with stable CAH due to NMD, RTCD, CRCD (congenital and acquired), and OHS. The scope of these NPPV titration recommendations is restricted to pressure preset BPAP ventilation by mask as this is the type of ventilatory support available in most sleep centers.

9. It is understood that the recommendations for minimum and maximum IPAP and EPAP may be constrained by the specific BPAP device used during the titration protocol. These recommendations should not be followed in a “cookbook” manner; instead, sleep technologists and clinicians should combine their experience and judgment with the application of these recommendations to attain the best possible titration for any given patient. Recommendations extracted from active AASM practice parameters are labeled “(Standard)” while those not based on published AASM practice parameters are labeled “(Consensus).” The indications, goals of treatment, rationale for use, and side effects of NPPV treatment should be discussed in detail with the patient prior to the NPPV titration study. Careful mask fitting and a period of acclimatization to low pressure before the titration should be included as part of the NPPV protocol. (Standard A)

10. NPPV titration with PSG is the recommended method to determine an effective level of nocturnal ventilatory support in patients with known daytime or nocturnal hypoventilation. In circumstances (based on clinical judgment) when NPPV treatment is initiated and adjusted empirically in the outpatient setting, a PSG should be utilized (if and when possible) to confirm that the final NPPV settings are effective or to make further adjustments as necessary. (Level A - Consensus). The stated goals of titration usually were to 1- Eliminate obstructive events and 2- Improve ventilation such that the SpO2 was > 90% and the transcutaneous PCO2 was less than a set goal (45 to 50 mm Hg), if sufficient pressure to achieve these goals was tolerated.

11. NPPV treatment can be initiated without PSG. A.In some situations, based on clinical judgment, treatment can be empirically initiated at low pressure settings. B.Treatment pressures are then increased as tolerated over days to weeks based on daytime PCO2 measurements, nocturnal oximetry, subjective relief of symptoms, and in some cases nocturnal transcutaneous PCO2 monitoring. Such an approach may be suitable when the patient has difficulty tolerating NPPV or the major treatment goal is palliation. C.Inpatient versus outpatient initiation of home mechanical ventilation in patients with nocturnal hypoventilation found equivalent outcomes.

12. Attended NPPV titration with PSG is the standard method to determine an effective level of NPPV support when the treatment goals are to: 1- Reduce sleep fragmentation and improve sleep quality 2-Decrease the work of breathing and provide respiratory muscle rest 3- Normalize or improve gas exchange, and 4- Relieve or improve nocturnal symptoms in patients with nocturnal hypoventilation. (Level A - Consensus). If palliation is the main goal, finding a tolerable level of NPPV that improved symptoms (nocturnal dyspnea, morning headache, frequent awakenings) would be the primary goal of NPPV titration and treatment. Evidence that NPPV has reduced work of breathing includes an increase in tidal volume, a reduction in respiratory rate, and absence or reduction of inspiratory EMG activity of the muscle of respiration compared to baseline levels or those on lower amounts of NPPV support.

13. In instances where OSA coexists with CAH NPPV titration with PSG is the standard method to determine effective pressure settings for the treatment of OSA. (Level A - Standard) The titration of positive airway pressure to eliminate obstructive events should follow the AASM Clinical Guidelines for PAP Titration in Patients with Obstructive Sleep Apnea. (Level A - Consensus). The majority of patients with the obesity hypoventilation syndrome have discrete apneas and hypopneas. Chronic hypoventilation due to chest wall disorders and neuromuscular disorders also were found to have obstructive respiratory events during PSG.

14. Attended NPPV titration with PSG is the standard method to identify optimal treatment pressure settings for patients with the OHS in whom NPPV treatment is indicated (Level A - Consensus). The majority of patients with OHS have obstructive sleep apnea. However, a minority simply have daytime hypoventilation that worsens during sleep in the absence of discrete obstructive events. Chronic CPAP treatment in OHS patients can also result in a reduction in daytime PCO2 in some patients.However, many OHS patients require high levels of CPAP and may manifest residual arterial oxygen desaturation or continue to hypoventilate after upper airway patency is restored. In such patients,BPAP (NPPV) has been proven effective and by augmenting ventilation may prevent the need for mechanical ventilation or supplemental oxygen. The mean IPAP and EPAP values were 18 and 8 cm H2O, respectively.

15. Attended NPPV titration with PSG is the recommended method to identify an effective level of ventilatory support for patients with RTCD in whom NPPV treatment is indicated. (Level A - Consensus). Most published studies concerning NPPV treatment in RTCD patients have not used an attended NPPV titration study to select levels of pressure. Treatment NPPV settings were based on daytime arterial blood gas testing, nocturnal oximetry, or nocturnal transcutaneous PCO2 monitoring. The mean IPAP and EPAP values were 21.1 and 3.1 cm H2O, respectively, with a backup rate of 20 bpm. improvement in daytime PCO2 was correlated with the amount of pressure support.

16. Attended NPPV titration with PSG should be performed before NPPV treatment in patients with acquired or congenital CRCD when NPPV treatment is deemed indicated. (Level A - Consensus). CRCD such as those with congenital central hypoventilation may have life-threatening events if not adequately ventilated during sleep. Patients with congenital central hypoventilation often require tracheostomy and volume ventilation from birth at least during sleep. A potential complication of early use of mask ventilation is development of central facial hypoplasia, possibly due to chronic mask pressure.

17. Attended NPPV titration with PSG allows definitive identification of an adequate level of ventilatory support for patients with NMD in whom NPPV treatment is planned. (Level A - Consensus). Initiating NPPV on an outpatient basis during the daytime can be done. NMD patients are often started on BPAP at low pressures (IPAP = 8, EPAP = 4) after a period of daytime adaptation under direct supervision. If patients tolerate nocturnal NPPV with low pressures, the settings are increased over weeks to months based on symptoms and/or daytime arterial PCO2 measurement (or end-tidal PCO2). Only 6/19 required a pressure support over 10 cm H2O. In patients with rapidly progressive NMD, the main goal of treatment is often palliation of symptoms and improvement in quality of life rather than normalization of nocturnal arterial PCO2.

18. The nppv device used for nppv titration should have the ability to function in the spontaneous [support] (s), spontaneous/timed [support/timed] (st), and timed (t) modes. ideally the device should provide analog or digital outputs of flow, pressure, leak, and tidal volume that may be recorded during polysomnography. (level a - consensus). Patients with OHS may not require a backup rate.Patients with severely defective central control of ventilatory drive often require a backup rate to prevent central apneas and/or hypoventilation. In patients with respiratory muscle weakness or decreased respiratory system compliance, feeble inspiratory efforts may fail to reliably trigger an IPAP/EPAP cycle; such patients often benefit from a backup rate. The timed mode is infrequently used in sleep centers. The timed mode employing a set respiratory rate that is typical higher than the native rate may result in a more stable pattern of ventilation in some patients. a relatively high respiratory rate of 20 was used in the timed mode, with an inspiratory/expiratory ratio of 1 to 2.

19. Back up rate The timed mode or the ST mode with a relatively high rate is an option that could be tried in patients who do not tolerate high IPAP or in whom the maximally tolerated pressure support at the spontaneous respiratory rate does not deliver adequate minute ventilation. This may be a particularly effective strategy in patients with RTCD and reduced respiratory system compliance, in whom a high PS may be required to augment tidal volume.

20. Recording the airflow signal directly obtained from the nppv device (derived from the accurate internal flow sensor) is the recommended method for monitoring airflow and detecting apneas and hypopneas during nppv titration. (level a - consensus) Measurement of airflow using a thermal device or a nasal pressure cannula under the mask is not recommended. thermal device signals are not proportional to flow, and a nasal pressure cannula may cause problems with the mask seal and result in undesired leak. (level a - consensus) Sawtooth patterns in the unfiltered inspiratory airflow or mask pressure tracings and/or detection of vibration by piezoelectric transducers or microphones applied to the neck are acceptable methods for detecting snoring during nppv titration (level a - consensus) The nppv device estimate of tidal volume derived from an accurate internal flow sensor is an acceptable method to estimate tidal volume. the tidal volume signal obtained from the nppv device should be recorded if possible. (level a -consensus)

21. The nppv device measurement of delivered pressure using an accurate internal pressure sensor is an acceptable method to estimate delivered pressure. measurement of pressure at the mask or device outlet using an accurate pressure transducer is also an acceptable method of determining delivered pressure. a signal reflecting delivered pressure (at the machine or mask) should be recorded if possible. (level a - consensus) Some NPPV devices output a brief signal (intentional artifact) before each machine triggered breath. Another method to identify machine triggered breaths is to observe that they often have a different inspiratory time than spontaneous breaths.

22. The nppv device measurement of leak using an internal flow sensor is an acceptable method to estimate leak. a signal reflecting leak should be monitored and recorded if possible. (level a - consensus). The total flow partitioned into a bias portion (leak) and a variable portion (patient flow). The leak is composed of the intentional leak + unintentional leak (mask or mouth leak). The intentional leak is due to flow through the non-rebreathing orifice. This leak depends on the interface type and delivered pressure. In some NPPV devices, the leak signal reflects the total leak; in others, a mask interface can be specified and the leak signal reflects unintentional leak. Leak,especially mouth leak, can impair the effectiveness of NPPV and sleep quality. As delivered pressure increases during the titration, the total leak will increase.

23. Recording respiratory muscle EMG activity using bipolar surface electrodes may be useful during NPPV titration in patients with NMD and/or an increased effort of breathing. adequate NPPV support for muscle rest is associated with the absence or decrease in inspiratory EMG activity of the respiratory muscles during NREM sleep. (level a - consensus) Surface diaphragm EMG recording utilizes two electrodes about 2 cm apart horizontally in the seventh and eighth intercostal spaces in the right anterior axillary line. The right side of the body is used to reduce ECG artifact. Other sites include the sternocleidomastoid and the right parasternal intercostal muscle (2nd and 3rd intercostal spaces in the mid-clavicular line). In patients with respiratory muscle weakness or increased work of breathing, the EMG of accessory muscles often shows inspiratory activity during NREM sleep. During the NPPV titration, a reduction in the EMG activity of respiratory muscles may be a useful indicator that sufficient pressure support is being administered to allow muscle rest.

24. Arterial blood gas testing at a given level of NPPV support (once settings have been optimized or in the morning after a night of NPPV) is the most accurate method for determining the effects of NPPV on the arterial Pco2 (level A - consensus) Determination of the arterial PCO2 by arterial blood gas sampling is the gold standard but is invasive, and arterial blood gas sampling requires special expertise. In addition, rapid access to a laboratory where the sample can be processed may be problematic for sleep centers located outside of hospital. Another limitation of arterial blood gas monitoring is that serial testing during sleep requires either an indwelling catheter or repeated arterial punctures, and obtaining a sample may well cause arousal and a change in the PCO2.

25. Transcutaneous co2 (Ptcco2) monitoring maybe useful for NPPV titration when the device is calibrated and the readings are within 10 mm hg of the concurrent Pco2 value obtained by ABG testing during stable breathing. due to A slow response time, changes in Ptcco2 generally are delayed following changes in the arterial Pco2 (level A - consensus) Certainly the information supplied by transcutaneous PCO2 may be very useful if the accuracy can be verified. PtcCO2 device is calibrated before monitoring and the results are validated by ABG sampling at least at the start of or during the study. Caution is advised in making clinical decisions based on transcutaneous PCO2 monitoring alone especially if the results do not correlate with other findings.

26. End-tidal Pco2 (PetPco2) monitoring may be useful during NPPV titration. The accuracy of Petco2 should be validated by concurrent Pco2 measurement using ABG testing during stable breathing. Petco2 values that differ by less than 10 mm hg from the arterial value indicate a valid reading. sampling of gas at the nares rather than at the mask is required for optimal measurement of Petco2 during NPPV titration. if the Plateau is lost from the Petco2 waveform during the titration, the measurement can no longer be considered accurate. if significant lung disease is Present, the difference between the Petco2 and the arterial Pco2 often exceeds 10 mm hg. for this reason, end-tidal Pco2 measurement is less frequently used in Patients with CAH who have significant concurrent lung disease. (level A - consensus). In the commonly used side-stream capnography method, exhaled gas is suctioned via a nasal cannula to an external CO2 sensor. The major challenge for end-tidal PCO2 monitoring during NPPV titration is dilution of the exhaled sample by flow from the NPPV device (especially if gas is sampled at the mask). One approach is to have the patient wear a sampling nasal cannula under the NPPV mask interface. Using this approach gas is sampled as it is exhaled from the nares rather than suctioned from the mask. A disadvantage of this approach is that the presence of the cannula passing under the nasal or oronasal mask seal could cause excessive leak. If an oral mask is used the sampling catheter would be directly connected to the mask.

27. There should be several different types of PAP interfaces (nasal masks, nasal pillows, oro-nasal mask) and accessories (chin straps, heated humidifier) available if the patient encounters problems (e.g., mouth leak, nasal congestion) during the night. the Patient should be acclimatized to the interface and the mask fit tested with the Pressure on Prior to “lights off.” (level A - consensus) Haeated humidification should be available for Patients undergoing NPPV titration. the addition of humidificaion is indicated if the patient complains of significant oral or nasal dryness (unless humidification is not tolerated by the patient). (level A - consensus). NPPV devices deliver air at a reduced relative humidity compared to ambient air and that increasing IPAP lowered the delivered relative humidity. Nava and coworkers compared heated humidification with a heat and moisture exchanger using a crossover protocol and found similar adherence to NPPV. Initiation of humidification at the start of a NPPV titration PSG may be useful in selected patients with significant nasal congestion or a history of severe mucosal dryness during sleep, or in particularly dry climates such as during the winter in cold climates.

28. The recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O,respectively. (Level A -Consensus). The recommended minimum starting pressure support (difference between IPAP and EPAP) should be 4 cm H2O.(Level A – Consensus). The recommended maximum pressure support (difference between IPAP and EPAP) should be 20 cm H2O. (Level A - Consensus). In the AASM clinical guidelines for titration of CPAP and BPAP, the recommended minimum IPAP-EPAP difference was 4 cm H2O and the maximum was 10 cm H2O. In the case of OSA, the major objective is to maintain airway patency. Budweiser and coworkers used a mean pressure support of 18 cm H2O in a study of patients with RTCD. Patients with low respiratory system compliance may require high level of pressure support to augment ventilation during sleep.

29. The recommended maximum IPAP should be 20 cm H2O for patients < 12 years and 30 cm H2O for patients ≥ 12 years. (Level A - Consensus) High pressure levels are problematic for obtaining an adequate mask seal and often require significant mask tightening. There have been reports of changes in facial structure associated with NPPV in children. The minimum and maximum incremental changes in PS during NPPV titration should be 1 and 2 cm H2O, respectively. (Level A - Consensus). Although smaller pressure changes than 1 cm H2O are possible, such changes are unlikely to be clinically meaningful. A maximum incremental change of 2 cm H2O is recommended to avoid over titration. IPAP and EPAP should be adjusted to eliminate obstructive apneas, hypopneas, RERAs, and snoring following the AASM Clinical Guidelines for the Manual Titration of PAP in Patients with OSA. (Level A – Consensus). The PS should be increased every 5 minutes if the tidal volume is below the acceptable goal. an acceptable tidal volume goal for most patients ranges from 6 to 8 ml/kg using ideal body weight. (level a - consensus)

30. The PS should be increased in 1 to 2 cm H2o increments if the trans- cutaneous pco2 or end-tidal pco2 remains 10mhg or more above goal for 10 minutes or more. this assumes that these measurements of the pco2 have been documented to accurately reflect the arterial pco2 in a given patient. (level a - consensus). Pressure support may be increased if respiratory muscle rest has not been achieved by nppv treatment at the current settings for 10 minutes or more. adequate respiratory muscle rest during nppv is associated with resolution or improvement in tachypnea and/or excessive inspiratory effort as measured by phasic EMG activity of inspiratory muscles. (level a – consensus) Pressure support may be increased if the spo2 remains below 90% for 5 minutes or more and tidal volume is low (<6 to 8 ml/kg). if discrete obstructive apneas or hypopneas are present, the clinical guidelines for pap titration in OSA patients should be followed. (level a - consensus).

31. The ST Mode (backup rate) should be used in all patients with central hypoventilation or significantly impaired respiratory drive. If the ST Mode is not successful the Timed Mode with a fixed respiratory rate may be tried (Level A - Consensus). The ST Mode (backup rate) should be used if frequent and significant central apneas are present at baseline or during the NPPV titration, if the respiratory rate is inappropriately low, or if the patient fails to reliably trigger the NPPV device to transition from EPAP to IPAP due to muscle weakness. If the ST Mode is not successful, the Timed Mode with a fixed respiratory rate may be tried (Level A - Consensus). The ST Mode (backup rate) may be used if adequate ventilation or adequate respiratory muscle rest is not achieved with the maximum (or maximum tolerated) PS in the spontaneous mode. If the ST Mode is not successful, the Timed Mode with a fixed respiratory rate may be tried. (Level A - Consensus). The starting backup rate for the ST mode should be equal to or slightly less than the patient’s spontaneous sleeping respiratory rate (minimum of 10 bpm). if the sleeping respiratory rate is not known, one may use the spontaneous awake respiratory rate. the initial setting for the respiratory rate in the timed mode should be equal or slightly less than the patient’s spontaneous sleeping respiratory rate or the current back-up rate if switching from the ST to timed mode. (level a – consensus)

32. The backup rate (ST mode) or specified respiratory rate (timed mode) should be increased in increments of 1-2 breaths per minute, no more frequently than every 10 minutes, if the desired goal of the backup rate (or fixed respiratory rate) is not attained with lower rates. (level a – consensus) The backup rate (ST mode) or respiratory rate (timed mode) should be decreased if the patient reports discomfort thought to be related to a high respiratory rate or if nppv device triggered and patient triggered breaths are frequently superimposed (stacking of breaths). (level a – consensus). The recommended % IPAP time is usually between 30% and 40%. the default inspiratory time on nppv devices is commonly 1.2 seconds. (level a - consensus). A shorter inspiratory time (%IPAP time of approximately 30%) may be useful in patients with concurrent obstructive airways disease (especially at higher respiratory rates) to allow adequate time for exhalation. a longer inspiratory time (%IPAP time of approximately 40%) may be useful in patients with restrictive disease such as RTCD (decreased respiratory system compliance). (level a - consensus).